US2016052912A1PendingUtilityA1

Diaminoheteroaryl substituted indazoles

Assignee: BAYER PHARMA AKITIENGESELLSCHAFTPriority: Mar 21, 2013Filed: Mar 19, 2014Published: Feb 25, 2016
Est. expiryMar 21, 2033(~6.6 yrs left)· nominal 20-yr term from priority
A61K 31/5377A61K 31/53A61K 31/506A61P 35/00A61K 45/06C07D 403/14A61K 31/695C07F 7/1804A61K 31/5383C07D 401/14C07D 403/04C07D 401/04C07D 498/04A61P 35/02
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Claims

Abstract

Compounds of formula (I) which are inhibitors of Bub 1 kinase, processes for their production and their use as pharmaceuticals.

Claims

exact text as granted — not AI-modified
1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         in which 
         X is CR 6 , N, 
         Y is CH, N, 
         R 1  is hydrogen, halogen, 1-3C-alkyl, 
         R 2 /R 3  are independently from each other hydrogen, halogen, cyano, hydroxy, 1-6C-haloalkyl, 1-6C-haloalkoxy, 1-6C-alkoxy, 
         R 4  is independently hydrogen, hydroxy, halogen, cyano, 1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, 1-6C-haloalkyl, 1-6C-hydroxyalkyl, 1-6C-alkoxy, —O-(2-4C-alkylen)-O—C(O)-(1-4C-alkyl), 1-6C-haloalkoxy, —C(O)OR 9 , —C(O)-(1-6C-alkyl), —C(O)NR 10 R 11 , 3-7C-cycloalkyl, —S(O) 2 NH-(3-6C-cycloalkyl), —S(O) 2 NR 10 R 11 ,
 heteroaryl which optionally is substituted independently one or more times with cyano, 1-4C-alkyl, 1-4C-haloalkyl, 1-4C-haloalkoxy, 
 whereby two of R 2 , R 3  (R 4 ) n , when positioned ortho to each other, may form together with the two carbon atoms to which they are attached, a heterocyclic 5-, 6- or 7-membered ring containing 1 or 2 heteroatoms selected from O or N, and optionally containing an additional double bond and/or optionally substituted by an oxo (═O) group and/or an 1-4C-alkyl group, 
 
         n 0, 1, 2 or 3 
         R 5  is (a) hydrogen;
 (b) —C(O)-(1-6C-alkyl); 
 (c) —C(O)-(1-6C-alkylen)-O-(1-6C-alkyl); 
 (d) —C(O)NH-(1-6C-alkyl); 
 (e) 
 
       
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 6  is (a) hydrogen;
 (b) hydroxy; 
 (c) cyano; 
 (d) 1-6C-alkoxy optionally substituted independently one or more times with
 (d1) OH, 
 (d2) —O-(1-6C-alkyl), 
 (d3) —C(O)NR 10 R 11 , 
 (d4) —NR 12 R 13 , 
 (d5) —S-(1-6C-alkyl), 
 (d6) —S(O)-(1-6C-alkyl), 
 (d7) —S(O) 2 -(1-6C-alkyl), 
 (d8) —S(O) 2 NR 10 R 11 , 
 (d9) heterocyclyl, which is optionally substituted with oxo (═O), 
 (d10) heteroaryl, which is optionally substituted independently one or more times with cyano, 1-4C-alkyl, 1-4C-haloalkyl, 1-4C-haloalkoxy, C(O)NR 10 R 11 , (1-4C-alkylen)-O-(1-4C-alkyl), 
 
 (e) —O-heteroaryl opt. subst. with CN, 
 (f) 
 
       
       
         
           
           
               
               
           
         
         
           whereby the * is the point of attachment, 
           (g) —O-(2-6C-alkylen)-O-(1-6C-alkyl) which is optionally substituted with hydroxy, 
           (h) —NR 12 R 13 , 
           (i) —NHS(O) 2 -(1-6C-alkyl), 
           (j) —NHS(O) 2 -(1-6C-haloalkyl), 
           or 
           optionally, R 5  and R 6  form a 6-membered ring together with the nitrogen atom to which R 5  is attached and together with the pyrimidine ring carbon atoms to which R 5 —NH and R 6  are attached which may contain one further heteroatom selected from the group consisting of O, S, N,
 and which is optionally substituted by an oxo (═O) group, 
 
         
         R 7  is
 (a) hydrogen, 
 (b) 1-4C-alkyl, which is optionally substituted with heteroaryl 
 (c) 1-4C-haloalkyl, 
 (d) 2-4C-hydroxyalkyl, 
 (e) 
 
       
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 8  is independently hydrogen, halogen, hydroxy, 1-4C-alkyl, 1-4C-hydroxyalkyl, 1-4C-haloalkyl, 1-4C-haloalkoxy, C(O)OR 9 , C(O)NR 10 R 11 , 
         m is 0, 1, 2, 3 or 4, 
         R 9  is
 (a) hydrogen, 
 (b) 1-4C-alkyl which optionally is substituted with hydroxy, 
 
         R 10 , R 11  are independently from each other hydrogen, 1-4C-alkyl, 2-4C-hydroxyalkyl,
 or 
 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring optionally containing one further heteroatom selected from the group consisting of O, S or N, and which is optionally substituted with 1-2 fluorine atoms or C(O)OR 9 , 
 
         R 12 , R 13  are independently from each other hydrogen, 1-4C-alkyl, 2-4C-hydroxyalkyl, —C(O)-(1-6C-alkyl), —C(O)-(1-6C-alkylen)-O-(1-6C-alkyl), —C(O)H, C(O)OR 9 ,
 or 
 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring optionally containing one further heteroatom selected from the group consisting of O, S or N, and which is optionally substituted by an oxo (═O) group, 
 
         or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer. 
       
     
     
         2 . The compound of formula (I) according to  claim 1 ,
 wherein   X is CR 6 , N,   Y is CH, N,   R 1  is hydrogen, halogen, 1-3C-alkyl,   R 2 /R 3  are independently from each other hydrogen, halogen, cyano, hydroxy, 1-3C-haloalkyl, 1-3C-haloalkoxy, 1-3C-alkoxy,   R 4  is independently hydrogen, hydroxy, halogen, cyano, 1-3C-alkyl, 2-3C-alkenyl, 2-3C-alkynyl, 1-3C-haloalkyl, 1-3C-hydroxyalkyl, 1-3C-alkoxy, —O-(2-4C-alkylen)-O—C(O)-(1-4C-alkyl), 1-3C-haloalkoxy, —C(O)OR 9 , —C(O)-(1-3C-alkyl), —C(O)NR 10 R 11 , 3-7C-cycloalkyl, —S(O) 2 NH-(3-6C-cycloalkyl), —S(O) 2 NR 10 R 11 ,   n 0, 1,   R 5  is (a) hydrogen;
 (b) —C(O)-(1-3C-alkyl); 
 (c) —C(O)-(1-3C-alkylen)-O-(1-3C-alkyl); 
 (d) —C(O)NH-(1-3C-alkyl); 
 (e) 
   
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 6  is (a) hydrogen;
 (b) hydroxy; 
 (c) cyano; 
 (d) 1-3C-alkoxy optionally substituted independently one or more times with
 (d1) OH, 
 (d2) —O-(1-3C-alkyl), 
 (d3) —C(O)NR 10 R 11 , 
 (d4) —NR 12 R 13 , 
 (d5) —S-(1-3C-alkyl), 
 (d6) —S(O)-(1-3C-alkyl), 
 (d7) —S(O) 2 -(1-3C-alkyl) 
 (d8) —S(O) 2 NR 10 R 11 , 
 (d9) heterocyclyl, which is optionally substituted with oxo (═O), 
 (d10) heteroaryl, which is optionally substituted independently one or more times with cyano, 1-4C-alkyl, 1-4C-haloalkyl, 1-4C-haloalkoxy, C(O)NR 10 R 11 , (1-4C-alkylen)-O-(1-4C-alkyl), 
 
 (e) —O-heteroaryl opt. subst. with CN, 
 (f) 
 
       
       
         
           
           
               
               
           
         
         
           whereby the * is the point of attachment, 
           (g) —O-(2-3C-alkylen)-O-(1-3C-alkyl) which is optionally substituted with hydroxy, 
           (h) —NR 12 R 13 , 
           (i) —NHS(O) 2 -(1-3C-alkyl), 
           (j) —NHS(O) 2 -(1-3C-haloalkyl), 
           or 
           optionally, R 5  and R 6  form a 6-membered ring together with the nitrogen atom to which R 5  is attached and together with the pyrimidine ring carbon atoms to which R 5 —NH and R 6  are attached which may contain one further heteroatom selected from the group consisting of O, S, N,
 and which is optionally substituted by an oxo (═O) group, 
 
         
         R 7  is
 (a) hydrogen, 
 (b) 1-4C-alkyl, which is optionally substituted with heteroaryl 
 (c) 1-4C-haloalkyl, 
 (d) 2-4C-hydroxyalkyl, 
 (e) 
 
       
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 8  is hydrogen, halogen, hydroxy, 1-4C-alkyl, 1-4C-hydroxyalkyl, 1-4C-haloalkyl, 1-4C-haloalkoxy, C(O)OR 9 , C(O)NR 10 R 11 , 
         m is 0, 1 
         R 9  is (a) hydrogen,
 (b) 1-4C-alkyl which optionally is substituted with hydroxy, 
 
         R 10 , R 11  are independently from each other hydrogen, 1-4C-alkyl, 2-4C-hydroxyalkyl,
 or 
 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring optionally containing one further heteroatom selected from the group consisting of O, S or N, and which is optionally substituted with 1-2 fluorine atoms or C(O)OR 9 , 
 
         R 12 , R 13  are independently from each other hydrogen, 1-4C-alkyl, 2-4C-hydroxyalkyl, —C(O)-(1-3C-alkyl), —C(O)-(1-3C-alkylen)-O-(1-3C-alkyl), —C(O)H, C(O)OR 9 ,
 or 
 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring optionally containing one further heteroatom selected from the group consisting of O, S or N, and which is optionally substituted by an oxo (═O) group, 
 
         or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer. 
       
     
     
         3 . The compound of formula (I) according to  claim 1 ,
 wherein   X is CR 6 , N,   Y is CH, N,   R 1  is hydrogen, halogen, 1-3C-alkyl,   R 2 /R 3  are independently from each other hydrogen, halogen, cyano, hydroxy, 1-3C-haloalkyl, 1-3C-haloalkoxy, 1-3C-alkoxy,   R 4  is independently hydrogen, hydroxy, halogen, cyano, 1-3C-alkyl, 2-3C-alkenyl, 2-3C-alkynyl, 1-3C-haloalkyl, 1-3C-hydroxyalkyl, 1-3C-alkoxy, 1-3C-haloalkoxy, —C(O)OR 9 , —C(O)-(1-3C-alkyl), —C(O)NR 10 R 11 , —S(O) 2 NR 10 R 11 ,   n 0, 1,   R 5  is (a) hydrogen;
 (b) —C(O)-(1-3C-alkyl); 
 (c) —C(O)-(1-3C-alkylen)-O-(1-3C-alkyl); 
 (d) —C(O)NH-(1-3C-alkyl); 
 (e) 
   
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 6  is (a) hydrogen;
 (b) hydroxy; 
 (c) cyano; 
 (d) 1-3C-alkoxy optionally substituted independently one or more times with
 (d1) OH, 
 (d2) —O-(1-3C-alkyl), 
 (d3) —C(O)NR 10 R 11 , 
 (d4) —NR 12 R 13 , 
 (d5) —S-(1-3C-alkyl), 
 (d6) —S(O)-(1-3C-alkyl), 
 (d7) —S(O) 2 -(1-3C-alkyl) 
 (d8) —S(O) 2 NR 10 R 11 , 
 (d9) heterocyclyl, which is optionally substituted with oxo (═O), 
 (d10) heteroaryl, which is optionally substituted independently one or more times with cyano, 1-4C-alkyl, 1-4C-haloalkyl, 1-4C-haloalkoxy, C(O)NR 10 R 11 , (1-4C-alkylen)-O-(1-4C-alkyl), 
 
 (e) —O-heteroaryl opt. subst. with CN, 
 (f) 
 
       
       
         
           
           
               
               
           
         
         
           whereby the * is the point of attachment, 
           (g) —O-(2-3C-alkylen)-O-(1-3C-alkyl) which is optionally substituted with hydroxy, 
           (h) —NR 12 R 13 , 
           (i) —NHS(O) 2 -(1-3C-alkyl), 
           (j) —NHS(O) 2 -(1-3C-haloalkyl), 
           or 
           optionally, R 5  and R 6  form a 6-membered ring together with the nitrogen atom to which R 5  is attached and together with the pyrimidine ring carbon atoms to which R 5 —NH and R 6  are attached which may contain one further heteroatom selected from the group consisting of O,
 and which is optionally substituted by an oxo (═O) group, 
 
         
         R 7  is
 (a) hydrogen, 
 (b) 1-4C-alkyl, which is optionally substituted with heteroaryl 
 (c) 1-4C-haloalkyl, 
 (d) 2-4C-hydroxyalkyl, 
 (e) 
 
       
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 8  is hydrogen, halogen, hydroxy, 1-4C-alkyl, 1-4C-hydroxyalkyl, 1-4C-haloalkyl, 1-4C-haloalkoxy, C(O)OR 9 , C(O)NR 10 R 11 , 
         m is 0, 
         R 9  is (a) hydrogen, 
         (b) 1-4C-alkyl which optionally is substituted with hydroxy, 
         R 10 , R 11  are independently from each other hydrogen, 1-4C-alkyl, 2-4C-hydroxyalkyl,
 or 
 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring optionally containing one further heteroatom selected from the group consisting of O, S or N, and which is optionally substituted with 1-2 fluorine atoms or C(O)OR 9 , 
 
         R 12 , R 13  are independently from each other hydrogen, 1-4C-alkyl, 2-4C-hydroxyalkyl, —C(O)-(1-3C-alkyl), —C(O)-(1-3C-alkylen)-O-(1-3C-alkyl), —C(O)H, C(O)OR 9 ,
 or 
 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring optionally containing one further heteroatom selected from the group consisting of O 
 
         or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer. 
       
     
     
         4 . The compound of formula (I) according to  claim 1 ,
 wherein   X is CR 6 , N,   Y is CH, N,   R 1  is hydrogen,   R 2 /R 3  are independently from each other hydrogen, halogen,   R 4  is independently hydrogen, 1-3C-alkoxy,   n 0, 1,   R 5  is (a) hydrogen;
 (b) —C(O)-(1-3C-alkyl); 
 (c) —C(O)-(1-3C-alkylen)-O-(1-3C-alkyl); 
 (d) —C(O)NH-(1-3C-alkyl); 
 (e) 
   
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 6  is (a) hydrogen;
 (d) 1-3C-alkoxy optionally substituted independently one or more times with
 (d1) OH, 
 (d2) —O-(1-3C-alkyl), 
 
 (h) NR 12 R 13 , 
 (i) —NHS(O) 2 -(1-3C-alkyl), 
 (j) —NHS(O) 2 -(1-3C-haloalkyl), 
 or 
 optionally, R 5  and R 6  form a 6-membered ring together with the nitrogen atom to which R 5  is attached and together with the pyrimidine ring carbon atoms to which R 5 —NH and R 6  are attached which may contain one further heteroatom selected from the group consisting of O,
 and which is optionally substituted by an oxo (═O) group, 
 
 
         R 7  is
 (a) hydrogen, 
 ((e) 
 
       
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 8  is hydrogen, 
         m is 0, 
         R 12 , R 13  are independently from each other hydrogen, —C(O)-(1-3C-alkylen)-O-(1-3C-alkyl),
 or 
 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring optionally containing one further heteroatom selected from the group consisting of O 
 
         or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer. 
       
     
     
         5 . The compound of formula (I) according to  claim 1 ,
 wherein   X is CR 8 , N,   Y is CH, N,   R 1  is hydrogen,   R 2 /R 3  are independently from each other hydrogen, fluorine,   R 4  is independently hydrogen, 1-3C-alkoxy,   n 0, 1,   R 5  is (a) hydrogen;
 (b) —C(O)—CH 3 , 
 (c) —C(O)-(methylen)-O-(methyl); 
 (d) —C(O)NH-(1-3C-alkyl); 
 (e) 
   
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 6  is (a) hydrogen;
 (d) 1-3C-alkoxy optionally substituted independently one or more times with
 (d1) OH, 
 (d2) —O-(methyl), 
 
 (h) —NR 12 R 13 , 
 (i) —NHS(O) 2 -(1-3C-alkyl), 
 (j) —NHS(O) 2 —(CF 3 ), 
 or 
 optionally, R 5  and R 6  form a 6-membered ring together with the nitrogen atom to which R 5  is attached and together with the pyrimidine ring carbon atoms to which R 5 —NH and R 6  are attached which may contain one further oxygen atom, 
 and which is optionally substituted by an oxo (═O) group, 
 
         R 7  is
 (a) hydrogen, 
 (e) 
 
       
       
         
           
           
               
               
           
         
         
           whereby 
           the * is the point of attachment; 
         
         R 8  is hydrogen, 
         m is 0, 
         R 12 , R 13  are independently from each other hydrogen, —C(O)-(1-3C-alkylen)-O-(1-3C-alkyl),
 or 
 together with the nitrogen atom to which they are attached form a 6-membered heterocyclic ring containing one further oxygen atom 
 
         or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer. 
       
     
     
         6 . A compound of formula (I) according to  claim 1 , which is selected from the group consisting of:
 2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidine-4,6-diamine,   2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-N,N′-di(pyridin-4-yl)pyrimidine-4,6-diamine,   N-{2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-6-(pyridin-4-ylamino)-pyrimidin-4-yl}acetamide,   N-{2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-6-(pyridin-4-ylamino)pyrimidin-4-yl}-2-methoxyacetamide,   N-{6-(dipyridin-4-ylamino)-2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-pyrimidin-4-yl}acetamide,   N-{6-(dipyridin-4-ylamino)-2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]pyrimidin-4-yl}-2-methoxyacetamide,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)-pyrimidine-4,6-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidine-4,6-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(morpholin-4-yl)-N-(pyridin-4-yl)pyrimidine-4,6-diamine,   1-{2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(morpholin-4-yl)-6-(pyridin-4-ylamino)pyrimidin-4-yl}-3-ethylurea,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-N-(pyrimidin-4-yl)pyrimidine-4,6-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxy-N-(pyrimidin-4-yl)pyrimidine-4,6-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(morpholin-4-yl)-N-(pyrimidin-4-yl)pyrimidine-4,6-diamine,   1-{2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(morpholin-4-yl)-6-(pyrimidin-4-ylamino)pyrimidin-4-yl}-3-ethylurea,   6-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)-1,3,5-triazine-2,4-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(2-methoxyethoxy)-N-(pyridin-4-yl)pyrimidine-4,6-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(2-methoxyethoxy)-N-(pyrimidin-4-yl)pyrimidine-4,6-diamine,   N-{4-amino-2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-6-(pyridin-4-ylamino)pyrimidin-5-yl}-2-methoxyacetamide,   N-{4-amino-2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-6-(pyrimidin-4-ylamino)pyrimidin-5-yl}-2-methoxyacetamide,   N-{4-amino-2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-6-(pyridin-4-ylamino)pyrimidin-5-yl}ethanesulfonamide,   N-{4-amino-2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-6-(pyridin-4-ylamino)pyrimidin-5-yl}-1,1,1-trifluoromethanesulfonamide   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)-6H-pyrimido[5,4-b][1,4]oxazin-7(8H)-one,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-4-(pyrimidin-4-ylamino)-6H-pyrimido[5,4-b][1,4]oxazin-7(8H)-one,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-N,N′-di(pyridine-4-yl)pyrimidine-4,6-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxy-N,N′-di(pyridin-4-yl)pyrimidine-4,6-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(morpholin-4-yl)-N,N′-di(pyridin-4-yl)pyrimidine-4,6-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(morpholin-4-yl)-N,N′-di(pyrimidin-4-yl)pyrimidine-4,6-diamine,   6-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-N,N′-di(pyridin-4-yl)-1,3,5-triazine-2,4-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(2-methoxyethoxy)-N,N′-di(pyridin-4-yl)pyrimidine-4,6-diamine,   2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-(2-methoxyethoxy)-N,N′-di(pyrimidin-4-yl)pyrimidine-4,6-diamine,   N-{2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-4,6-bis(pyridin-4-ylamino)pyrimidin-5-yl}-2-methoxyacetamide,   N-{2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-4,6-bis(pyrimidin-4-ylamino)pyrimidin-5-yl}-2-methoxyacetamide,   N-{2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-4,6-bis(pyridin-4-ylamino)pyrimidin-5-yl}ethanesulfonamide,   N-{2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-4,6-bis(pyridin-4-ylamino)pyrimidin-5-yl}-1,1,1-trifluoromethanesulfonamide,   2-({4-amino-2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-6-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)ethanol, and   2-({2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-4,6-bis-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)ethanol,   
       or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer. 
     
     
         7 . (canceled) 
     
     
         8 . A method for the treatment of a hyperproliferative disease or disorder responsive to induction of cell death comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to  claim 1  or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer. 
     
     
         9 . The method according to  claim 8 , wherein the hyperproliferative disease or disorder responsive to induction of cell death is selected from haemotological tumours, solid tumours and metastases thereof. 
     
     
         10 . The method according to  claim 9 , wherein the tumor is selected from cervical tumors and metastases thereof. 
     
     
         11 . A pharmaceutical composition comprising a compound according to  claim 1  or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer, together with at least one pharmaceutically acceptable auxiliary. 
     
     
         12 . (canceled) 
     
     
         13 . A combination comprising a compound according to  claim 1  or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer, and an additional active ingredient selected from chemotherapeutic anti-cancer agents and target-specific anti-cancer agents. 
     
     
         14 . A compound selected from: 
       
         
           
           
               
               
           
         
         whereby R 1 , R 2 , R 3  R 4  R 6  and n have the meaning according to  claim 1 ; 
       
       
         
           
           
               
               
           
         
         whereby R 1 , R 2 , R 3  R 4  and n have the meaning according to  claim 1 ; 
       
       
         
           
           
               
               
           
         
         whereby R 1 , R 2 , R 3 , R 4  and n have the meaning according to  claim 1 ; 
       
       
         
           
           
               
               
           
         
         whereby R 1 , R 2 , R 3 , R 4  and n have the meaning according to  claim 1 . 
       
     
     
         15 . (canceled)

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